An RT Overview of the Revised PARDS Guidelines from PALICC II

The following is a transcript of the live webinar An RT Overview of the Revised Pediatric Acute Respiratory Distress Syndrome (PARDS) Guidelines from PALICC II, presented by Evan Richards, BSc, RT.

It is recommended that you download the course handout to supplement this text format.

Learning Outcomes

After this course, participants will be able to:

• Identify the key revisions in the Pediatric Acute Respiratory Distress Syndrome (PARDS) guidelines from PALICC II and understand their implications for clinical practice.
• Explain how to apply the revised PARDS guidelines in real-world scenarios, enhancing clinical decision-making and patient management skills in pediatric respiratory care.
• Discuss strategies to implement the updated guidelines effectively, aiming to improve patient outcomes through evidence-based respiratory therapy practices.

Introduction

I appreciate the opportunity to present this material, and I want to acknowledge that people take time out of their day to learn. That means a great deal to me. Everything I am about to share with you is based on clinical recommendations from evidence-based medicine, largely from randomized controlled trials or smaller individual trials. All content is evidence-based, and you will see why that matters when it comes to establishing guidelines.

Before going any further, let me simplify the terminology. Pediatric Acute Respiratory Distress Syndrome will be referred to throughout as PARDS, and the Pediatric Acute Lung Injury Consensus Conference will be called PALICC. The first consensus conference, PALICC 1, took place in 2015. The second, PALICC 2, was completed in 2023, and the revised guidelines it produced are the focus of this course.

I would like to acknowledge four colleagues whose contributions were essential to this presentation: Alex Rotta, MD, from Duke University; Robi Khemani, MD, the senior author of the PALICC 2 guidelines, from Children's Hospital Los Angeles; Ira Cheifetz, MD, from Rainbow Babies in Cleveland; and Martin Kneyber, MD, from Beatrix Children's Hospital in the Netherlands. I could not have assembled this content without them.

Why Children Are Not Small Adults

For many years, clinicians managed pediatric patients with ARDS by applying adult definitions and protocols to children. This approach is fundamentally flawed. Children are not small adults, and the physiological differences between children and adults have profound implications for how ARDS must be defined and managed.

Key physiological distinctions include the following.

• Airway cartilage formation is incomplete in children, whereas it is fully established in adults.
• Children have greater airway resistance due to smaller airways, making them more resistant to gas flow in both directions.
• Children have greater chest wall compliance because ossification of the rib cage is not yet complete, whereas the adult rib cage is solidified.
• Respiratory muscle reserve differs: children rely more heavily on the diaphragm than adults do.
• Pulmonary vascular resistance is a significantly greater problem in children, whose lungs are still growing and whose alveolar capillary proliferation is incomplete.
• Alveolar maturation differs dramatically: a child may have 20 to 50 million alveoli, resulting in a lower functional residual capacity, compared to approximately 500 million alveoli in a healthy adult.

These differences make it essential that pediatric ARDS be defined and managed on its own terms, not as a scaled-down version of adult ARDS.

What Is PARDS and Why Does It Matter?

Prior to 2015, there had never been a pediatric-specific definition of ARDS. Existing definitions, including the American-European Consensus Conference definition from 1994, the Murray Acute Lung Injury Score from 1998, the Delphi Consensus definition from 2005, and the Berlin definition from 2012, were all designed for adult populations.

Although PARDS affects only about 6 to 10 percent of patients in the pediatric intensive care unit, these patients consume approximately 80 percent of the unit's time and resources. They are, by definition, among the sickest children in any PICU. This clinical burden makes it essential to develop sound, evidence-based guidelines for their management.

The causes of PARDS are numerous. Sepsis and infectious pneumonia, bronchiolitis, aspiration, major trauma, pulmonary contusion, burns, inhalational injury, massive transfusions, transfusion-related acute lung injury, acute pancreatitis, fat embolism, envenomation, drowning, drug reactions, malignancy, and lung transplantation can all trigger PARDS. Regardless of the initiating cause, every one of these conditions presents a ventilation challenge that demands a carefully considered approach.

How PARDS Develops: Pathophysiology

In a healthy lung, each alveolus contains a layer of surfactant produced by type 2 pneumocytes. This surfactant maintains appropriate surface tension to keep the alveolus inflated. A basement membrane protects the alveolar wall. Capillaries remain close to the alveolar surface, enabling good ventilation-perfusion matching, and alveolar macrophages remain relatively quiescent.

When a patient becomes critically ill and requires mechanical ventilation, the shear forces generated by the ventilator can slough bronchial epithelium, denude the basement membrane, and create stress fractures in alveolar tissue. Interstitial flooding leads to protein-rich edema, which inactivates surfactant. Disrupted apoptosis impairs normal cellular renewal. Fibrin collects within alveolar walls, and gap formations develop in capillary walls under the pressure and volume delivered by the ventilator.

Once blood enters the air spaces or air enters the tissue spaces, an inflammatory cascade is triggered. Activated alveolar macrophages release interleukins and tumor necrosis factor, which act as chemoattractants for neutrophils. Neutrophils migrate into the lung from the bloodstream and, in attempting to contain the injury, release oxidants, leukotrienes, and proteases. The result is the full clinical picture of PARDS.

PALICC 1 (2015): The First Pediatric ARDS Consensus

In response to the absence of pediatric-specific ARDS guidelines, the first Pediatric Acute Lung Injury Consensus Conference convened. PALICC 1, completed in 2015, brought together 27 experts from eight countries. It was the first attempt to define ARDS specifically for pediatric patients. Over approximately three years, the group produced nine sections of guidance and more than 151 recommendations. The evidence base drew from both adult data and infant data, including studies conducted in neonatal intensive care units.

PALICC 2 (2023): An Expanded Effort

PALICC 2 was far more ambitious in scope. The consensus group expanded to 56 experts representing 15 countries across six continents. Forty-one percent of the participants were women, a significant increase from 2015. For the first time in either consensus conference, a respiratory therapist was included among the experts: Natalie Napolitano, MPH, RRT-NPS.

The process began in 2019 and was completed in 2023. The group conducted a systematic literature review to identify, assess, and combine all available evidence from adult randomized controlled trials, pediatric studies, and meta-analyses. Critically, no perinatal or neonatal data were included, reflecting the recognition that children are also not premature infants. The GRADE framework (Grading of Recommendations, Assessment, Development, and Evaluation) was used to classify each recommendation as either weak or strong. A strong recommendation required at least 96 percent agreement among participants after up to three rounds of voting. The final product comprised 11 sections and more than 160 recommendations.

Two new sections were added that had not existed in PALICC 1. The first addressed noninvasive respiratory support, reflecting the dramatically expanded use of noninvasive ventilation in pediatric critical care since 2015. The second addressed implementation in resource-limited settings, recognizing that not all centers have access to advanced equipment, full staffing, or the complete range of ventilatory options available in major teaching hospitals.

One inherent challenge for any PARDS guideline is the extraordinary range of patients it must cover. A pediatric patient with ARDS may be a young infant or a 17-year-old adolescent. Achieving consensus recommendations that apply meaningfully across this entire age spectrum is part of why strong recommendations require such a high level of agreement.

The Updated PARDS Definition

The core elements of the PARDS definition remained unchanged between PALICC 1 and PALICC 2. A patient with an oxygen index (OI) greater than 4, or an oxygen saturation index (OSI) greater than 5, should be considered at risk for PARDS. The major addition in PALICC 2 was the formal inclusion of a definition for noninvasive patients who cannot have an OI calculated because they do not have a measured mean airway pressure.

PALICC 2 also introduced an important change regarding the timing of diagnosis. Clinicians should not diagnose PARDS immediately upon a patient's arrival. Instead, the patient should be given four or more hours to stabilize with appropriate support before the diagnosis is made. The rationale is that modern therapists using modern equipment have become quite effective at rapidly stabilizing these patients. Premature diagnosis risks overloading a child with intervention before it is clear how sick that child truly is.

Severity Classification

PALICC 1 defined mild and moderate PARDS as separate categories. PALICC 2 combined them into a single category, because the data show very little difference in mortality rates between the two groups. Treating them separately created a false distinction in a population that is uniformly high-risk.

For intubated patients, mild to moderate PARDS is defined as an OI less than 16 or an OSI less than 12. Severe PARDS is defined as an OI of 16 or greater, or an OSI of 12 or greater. These thresholds are unchanged from PALICC 1.

For noninvasive patients, the PF ratio (PaO2 divided by FiO2) is used in place of the OI. A PF ratio greater than 100 indicates mild to moderate PARDS, while a PF ratio of 100 or less indicates severe PARDS.

To calculate the OI for an intubated patient, multiply the FiO2 (expressed as a decimal) by the mean airway pressure, divide by the PaO2, then multiply by 100. For example, a patient on 65 percent oxygen with a mean airway pressure of 16 and a PaO2 of 82 yields an OI of 12.5, placing that patient in the mild to moderate category. If that same patient deteriorates to 90 percent oxygen, a mean airway pressure of 19, and a PaO2 of 72, the OI rises to 24, indicating severe PARDS.

Resource-Limited Settings

PALICC 2 added guidance for resource-limited settings where full imaging, conventional mechanical ventilation, or adequate staffing may not be available. In these settings, a patient who requires supplemental oxygen to maintain an SpO2 of 88 percent or greater should be considered at risk for PARDS. Possible PARDS is defined by high-flow nasal cannula use at 1.5 L/kg/min or 30 L/min, or by a PF ratio of 300 or less, or an SF ratio of 250 or less in a patient on nasal noninvasive ventilation.

These patients are extremely high-risk. Approximately 50 percent of PARDS patients managed on noninvasive support ultimately require intubation, and those who do have very high mortality rates. Noninvasive ventilation in this population must be approached as a time-limited trial, with active monitoring for physiological stability including heart rate, respiratory rate, oxygenation, and work of breathing. If a patient with severe PARDS does not improve on noninvasive support, intubation should be pursued within one hour. For mild to moderate PARDS, a trial of four to six hours is appropriate before escalating to intubation. Resource-limited centers should also ensure they have a system in place for transferring patients who require a higher level of care.

Tidal Volume

PALICC 1 recommended a tidal volume (VT) of 5 to 8 mL/kg for patients with better respiratory system compliance, and 3 to 6 mL/kg for those with poor compliance. PALICC 2 updated this guidance based on a rigorous review of the evidence.

A landmark 1998 study by Amato and colleagues compared conventional ventilation using a VT of 12 mL/kg against a more protective strategy with a VT of 6 mL/kg. Patients on 12 mL/kg had a survival rate of approximately 28 percent. Those on 6 mL/kg had a survival rate of approximately 60 percent, demonstrating clearly that protective ventilation saves lives.

A subsequent multicenter randomized controlled trial by Dr. Khemani and colleagues found that 6 to 8 mL/kg produced the highest survival rates. Dropping below 6 mL/kg was associated with worse outcomes, possibly due to inadequate alveolar ventilation.

PALICC 2 revised the tidal volume recommendation to 6 to 8 mL/kg, with strong agreement at 98 percent. For patients in whom these volumes would cause plateau or driving pressures to exceed recommended limits, a VT less than 6 mL/kg should be used. In the most severely ill patients where survival is the primary concern, VT less than 4 mL/kg may be used with caution.

PEEP Recommendations

PALICC 1 recommended moderately elevated PEEP levels of 10 to 15 cm H2O, with higher levels considered acceptable in severe PARDS. PALICC 2 moved to a more structured approach.

PALICC 2 endorsed the Low PEEP/High FiO2 table from the ARDS Network protocol, which provides specific FiO2 and PEEP combinations to achieve adequate oxygenation. The target SpO2 range is 88 to 97 percent. Clinicians should use the table to guide their FiO2 and PEEP selections, recognizing that a PEEP lower than what the ARDSnet protocol specifies for a given FiO2 level is associated with higher pediatric mortality. There was strong agreement on this point at 96 percent.

The FiO2/PEEP table provides the following general pairings: FiO2 of 30 percent pairs with a PEEP of 5; 40 percent with 6 to 8; 50 percent with 8 to 10; 60 percent with 10; 70 percent with 10 to 14; 80 percent with 14; 90 percent with 14 to 18; and 100 percent with 18 to 24.

Importantly, PEEP should not be raised in isolation. As the patient's compliance, tidal volume, and hemodynamics change, PEEP should be titrated accordingly. As oxygenation improves and FiO2 is weaned, PEEP should be weaned in parallel to track the table. Conversely, when adjusting PEEP upward, clinicians must monitor that plateau pressure and driving pressure do not exceed their recommended limits. There was 100 percent agreement on this principle.

Evidence from large-scale studies supports elevating PEEP as the most effective single strategy for reducing the relative risk of death in ARDS. Research comparing three approaches, raising PIP without changing PEEP, raising both PIP and PEEP to maintain driving pressure, and raising PEEP while holding PIP stable, found that the last approach produced the most stable and favorable outcomes.

Driving Pressure: A New Addition in PALICC 2

Driving pressure is entirely new to PALICC 2; it was not addressed in PALICC 1. Driving pressure is defined as the difference between plateau pressure and PEEP. It is calculated by performing a brief inspiratory pause of two to three seconds. During this pause, pressure drops slightly as the lung and circuit absorb the delivered volume. The pressure at the end of that pause is the plateau pressure, not the peak inspiratory pressure. Driving pressure equals plateau pressure minus PEEP.

PALICC 2 recommends keeping plateau pressure at or below 28 cm H2O, with low agreement at 92 percent. In patients with reduced chest wall compliance, plateau pressures of 29 to 32 cm H2O may be necessary. These values are unchanged from PALICC 1.

The new addition is a specific limit on driving pressure: it should not exceed 15 cm H2O, as measured under static conditions. Although this recommendation achieved only 82 percent agreement and is therefore categorized as very low agreement in the GRADE framework, the clinical rationale is compelling. The lower the driving pressure, the lower the alveolar strain, and the better the patient's outcomes.

Consider a patient on a PEEP of 9 with a plateau pressure of 24: the driving pressure is 15, which is exactly at the recommended limit. If PEEP is then increased to 12 to improve oxygenation, the plateau pressure may rise above 28, pushing the patient into the lung injury risk zone. The appropriate response is to lower the tidal volume, which will bring the plateau pressure and driving pressure back within acceptable limits.

In practice, the three variables of PEEP, tidal volume, and driving pressure must be managed together. Increasing PEEP may require a corresponding reduction in tidal volume to stay within driving pressure limits.

Noninvasive Ventilation

PALICC 1 contained no guidance on noninvasive ventilation (NIV). PALICC 2 added a dedicated section reflecting the significant expansion of NIV use in pediatric critical care over the intervening years.

Meta-analytic data reviewed by PALICC 2 consistently showed that noninvasive approaches, including CPAP and high-flow nasal cannula, favor outcomes compared to standard oxygenation therapy. PALICC 2 recommends a time-limited trial of NIV, specifically CPAP or BiPAP, for patients who do not have a clear indication for immediate intubation. There was 88 percent agreement on this recommendation.

However, the time-limited nature of this trial must be taken seriously. If a patient on NIV does not demonstrate clinical improvement within four to six hours, or shows signs of deterioration, intubation should occur. There was 94 percent agreement on this point. The rationale is important: even patients who are never intubated can develop chronic lung disease if they struggle on noninvasive support for too long. Prolonged effort without adequate mean airway pressure to maintain an open lung strategy leads to ongoing injury through a different mechanism.

I recall a Canadian respiratory therapist describing a patient who was managed on NIV for 24 days before the team finally decided to intubate. The first post-intubation chest radiograph revealed chronic lung disease, despite the patient having never been on a conventional ventilator. Prolonged struggle on NIV had produced the injury.

For resource-limited settings, PALICC 2 suggests using CPAP or high-flow nasal cannula over standard oxygen therapy for patients at risk for PARDS (92 percent agreement), and CPAP over high-flow nasal cannula for patients with possible PARDS (83 percent agreement).

P-SILI: Patient Self-Inflicted Lung Injury

P-SILI, or patient self-inflicted lung injury, is another concept that is entirely new to PALICC 2. Unlike ventilator-induced lung injury, P-SILI is driven by the patient's own spontaneous breathing effort. When spontaneous breathing is intensely labored, large swings in transpulmonary pressure are generated. These pressure swings create alveolar stress even in the absence of mechanical ventilation. The worse the lung compliance, the more severe the problem.

P-SILI can occur in patients on conventional mechanical ventilation as well as those on noninvasive support. A patient taking large unassisted breaths through a poorly calibrated ventilator circuit is effectively injuring himself with each breath. This is why monitoring work of breathing is so important in every PARDS patient. Signs of excessive respiratory effort may indicate the need for sedation, neuromuscular blockade adjustment, or a reassessment of the ventilatory strategy itself.

Before proceeding to sedation or neuromuscular blockade, it is worth evaluating whether the ventilatory strategy itself can be adjusted to reduce the patient's drive to breathe. If a patient is working hard against the ventilator, it may be that the ventilator is not meeting the patient's needs. Modifying the strategy may reduce the work of breathing without requiring additional pharmacological intervention.

Putting It All Together

When a patient arrives in the PICU and is placed on noninvasive support, the clinician should begin calculating SF ratios and monitoring work of breathing immediately. Targeted sedation, adequate nutrition, and fluid management should be established as standard practice. Oxygenation targets on noninvasive support are an SpO2 of 92 to 97 percent.

If the patient requires intubation, the OI becomes the primary severity measure. On invasive ventilation, the PALICC 2 framework directs clinicians to maintain plateau pressure at or below 28 cm H2O, driving pressure at or below 15 cm H2O, tidal volume at 6 to 8 mL/kg, and PEEP according to the ARDSnet Low PEEP/High FiO2 table. The SpO2 target shifts to 88 to 97 percent to avoid exposing the patient to excessive oxygen toxicity.

As the OI worsens and the patient's condition deteriorates, additional interventions may be considered. Tidal volume may be reduced to 4 to 6 mL/kg. Neuromuscular blockade, inhaled nitric oxide therapy, prone positioning, and recruitment maneuvers may all be appropriate depending on the clinical picture. High-frequency jet ventilation (HFJV) or high-frequency oscillatory ventilation (HFOV), while not receiving a formal recommendation in PALICC 2, are available options when standard approaches are insufficient. If all conventional and rescue strategies are failing, extracorporeal membrane oxygenation (ECMO) must be considered before the window for safe cannulation closes.

Recruitment Maneuvers and High-Frequency Jet Ventilation

Recruitment maneuvers aim to open collapsed lung units and stabilize them at an adequate PEEP. An approach supported by evidence involves delivering a pressure 5 to 8 cm H2O above PEEP, no more than 15 cm above, and sustaining that pressure for 20 to 30 seconds, followed by a brief release, and then repeating the maneuver three times. On a conventional ventilator, this is approximated using two- to three-second inspiratory pause times. The underlying mechanism is pendulluft flow: when the inspiratory pause is long enough, air redistributes from better-ventilated alveoli to adjacent collapsed units, promoting gradual recruitment. This effect does not occur with the very short inspiratory times often used in standard ventilation.

PALICC 1 stated that HFJV could not be recommended for the routine management of PARDS but acknowledged it as a possible option in patients with severe pulmonary air leak syndrome, with 64 percent agreement. PALICC 2 made no recommendation for or against high-frequency ventilation of any type, despite the existence of multiple published studies. Research published in 2015 and 2020 as well as a 2021 study in the Respiratory Care journal demonstrated that HFJV improves oxygenation indices, normalizes pH, reduces FiO2 requirements, and may reduce the need for ECMO in PARDS patients. These studies also suggested that starting HFJV before the condition becomes too severe produces the best results.

The absence of HFJV from PALICC 2 reflects a gap in the evidence rather than evidence of harm. This represents an area where respiratory therapy researchers can make a meaningful contribution ahead of future consensus development.

The most important message from PALICC 2 was articulated simply by Dr. Cheifetz: back to basics and protective ventilation. How a patient is ventilated must be as protective as possible. Maintaining lower driving pressures, optimizing PEEP, delivering appropriate tidal volumes, and using longer inspiratory times at lower pressures all contribute to a safer ventilatory approach. High-frequency ventilation, conceptually described as CPAP with a wiggle, takes this principle to its logical extreme by delivering mean airway pressure without high-volume, high-pressure excursions.

Summary

PALICC 2 represents a rigorous, methodologically sound advance in the management of pediatric ARDS. Key achievements include the use of a larger and more diverse expert group, the exclusion of neonatal data to focus specifically on pediatric populations, the consolidation of mild and moderate PARDS into a single category, a four-hour observation window before diagnosis, and the formal extension of guidance to noninvasive patients and resource-limited settings.

The core recommendations that respiratory therapists should carry into practice are the tidal volume target of 6 to 8 mL/kg, PEEP management guided by the ARDSnet Low PEEP/High FiO2 table, plateau pressure at or below 28 cm H2O, driving pressure at or below 15 cm H2O, and active monitoring of work of breathing to detect P-SILI. Time-limited trials of noninvasive support with a clear threshold for escalating to intubation are also central to the revised guidelines.

Many recommendations carry only low or very low certainty of evidence, primarily because insufficient pediatric-specific research exists. This is an opportunity and a call to action for respiratory therapists who wish to engage in research. The areas with the weakest evidence, including high-frequency ventilation and several adjunctive therapies, are precisely where new data would have the greatest impact. If you are involved in PARDS research, you are contributing directly to the evidence base that will inform PALICC 3.

Questions and Answers

Given the broad age range of pediatric patients, from infants to adolescents, is it surprising that such a high level of agreement was required to achieve a strong recommendation?

That is an important point. The age range is precisely why strong recommendations are so difficult to achieve. The variability in patient size, developmental stage, and pathophysiology across the pediatric spectrum means that a recommendation which applies well to a one-year-old may not apply equally well to a fifteen-year-old. The requirement for 96 percent or greater agreement likely reflects this challenge. It is very hard to achieve near-universal consensus when the patient population is so heterogeneous.

What areas of PARDS research would you most encourage respiratory therapists to pursue?

The best strategy is to look at the PALICC 2 guidelines themselves and identify the sections where the recommendations carry the weakest evidence. Those are the areas where new research would have the greatest impact. High-frequency ventilation is a clear example: it received a strong recommendation in PALICC 1 only for air leak syndrome, received no consideration at all in PALICC 2, and yet multiple published studies suggest clinical benefit. That gap between available evidence and guideline inclusion represents an opportunity. More broadly, any section of the guidelines where the certainty of evidence is categorized as low or very low is a candidate for future study. Respiratory therapists who engage in this research will be among the heroes of PALICC 3.

References

References are provided in the course handout.